Cancer is a disease that seriously jeopardizes the health of human beings. Around the globe, about 6 million people die of cancer every year, with another 10 million on the brink of death. According to the estimate of the World Health Organization, in the 21st century, cancer will become the “number one killer” of mankind. The national retrospective investigation on the causes of death showed that in the past two decades, the morbidity and death rate of cancer in China have been on the rise year by year. Out of every five people died of disease, one was of cancer; for every 200 families, one suffered the pain of having a family member with cancer.
In the past several decades, many ways of treating cancer became available, mainly including surgery, radiotherapy, chemotherapy, hormonotherapy, gene therapy, and immunotherapy, among which surgery, radiotherapy and chemotherapy have became the major means. Chemotherapy refers to treating cancer with chemical medication. It is the field of the most rapid development in the diagnosis and treatment of cancer. A great number of new medicines aiming at different targets are ready for clinical application, and developments in research in mechanism of drug action and pharmacokinetics have made the clinical administration routes and means more fitting for killing tumor cells while protecting the normal tissues.
At present, pharmaceutical for chemotherapy mainly includes: pharmaceutical that affects the biosynthesis of nucleic acid, e.g. fluorouracil, 6-oxypurine, amethopterin, cytarabine, hydroxyurea; pharmaceutical that directly destroys DNA and prevents its reproduction, e.g. alkylating agents; antineoplastic antibiotics, e.g. Cisplatin and Carboplatin; pharmaceutical that interferes with the transcription and prevents the synthesis of RNA, e.g. actinomycin D, adriamycin, and other transcription restraining antibiotics; pharmaceutical that affects the synthesis of protein, e.g. catharanthines, podophyllotoxins, harringtonine, asparaginase; hormones, e.g. adrenal cortical hormone, estrogen, androgen, tamoxifen, aminoglutethimide. The existing chemotherapies and radiotherapies that are commonly used in treating cancer may cause serious toxic and other side effects that are adverse to the human body.
The property of interfering the polymerization or depolymerizaion of microtubulin of many natural medicines is regarded as having antineoplastic activity. Such medicines include vincristine, taxanes, and macrolide antineoplastic drugs. Microtubules play an important role in cell division, and the development of microtubulin binding factors is based on their capability of interfering cell proliferation. The depolymerizing factor of microtubulin, such as colchicine and vincristine, has the antimitotic effect, causing the tumor vessels to close. However, such effect of closing the tumor vessels only occurs when the dosage approaches the MTD (maximum tolerated dose). Endostatin, the latest discovered inhibiting factor of vasculogenesis, has the inhibiting effect on new vasculogenesis, but has no obvious effect on existing vessels or obvious target effect on tumor vessels.
A new type of microtubulin depolymerizing factor discovered in recent years can solve this problem by closing the vessels with dosage well below the MTD (Expert Opin Investig Drugs. 2004 September; 13 (9) 1171-82). In 2005, Loïc Vincent et al. mentioned a new type of microtubulin depolymerizing factor with similar property destroying microtubulin skeleton as vascular targeting factors (VTAs). Literature data shows that VTAs can selectively induce the decay of tumor vessels, partly through the VE-cadherin signal channel. This kind of microtubulin depolymerizing factor selectively destroys tumor vessels and prevent new vasculogenesis in the tumor while having no influence on the normal vascular system. At the same time, it can inhibit the polymerization of microtubulin, selectively cause tumor vessel function disorder and structural damage, and induce the apoptosis of vessel endothelial cells, playing its role of killing tumor cells or inhibiting tumor metastasis by making tumor cells lose the support of nutrition and oxygen.
In 2005, Gillian M. Tozer et al. reported in an influential journal, Nature Rev Cancer, that this kind of compound not only affects the proliferation of endothelial cells, but also influences their migration, quickly changing the pattern of endothelial cells, causing their apoptosis, and breaking their connections, so as to immediately cause the tumor vessel function disorder and structural damage. As the normal vessels are generally supported by smooth muscle cells, this kind of compound only affects the vessels without such support and has no influence on vessels supported by smooth muscle cells, it can quickly and selectively cause the tumor vessel function disorder and structural damage, thus affecting the tumor cells selectively (Nat Rev Cancer. 2005 June; 5(6) 423-35, J. Clin. Invest., Nov. 1, 2005; 115(11): 2992-3006). 2992-3006). At present, this type of medication is regarded as one of the most promising antineoplastic medicines.
Now Combretastatin A-4 is the only medicine of this kind that is under research overseas, whose research has entered the clinical stage. Through double bond connection, the most effective configuration in the stilbene units of Combretastatin to destroy tumor vessels is its cis-configuration, and the stilbene compound of trans-configuration has no inhibiting effect on tumors. It is very easy for reactions such as isomerization to take place due to the existence of cis, trans isomerism. The trans-configuration not only lacks efficacy, but also brings certain toxic side effects at the same time (for Combretastatin A-4, LD50 is 500 mg/kg), resulting in great difficulty in the preservation and actual application of Combretastatin A-4.
3,4,5,4′-tetramethoxyl-α,β-diphenylethane-3′-O-sodium sulphate of this invention is a synthesized compound, its structural formula being the following formula (I):

It is an entirely new chemical substance as well as a tumor vessel inhibitor of entirely new structure innovated and developed by the inventor. Unlike Combretastatin A-4, the two benzene rings are connected by single bond, which results in the differences in structure, conformation, bonding force, and trans effect between 3,4,5,4′-tetramethoxyl-α,β-diphenylethane-3′-O-sodium sulphate and Combretastatin A-4, greatly increasing the stability of compound (Light may isomerize Combretastatin A-4 to trans-configuration, so it should be kept out of light) and the effect over microtubulin.
3,4,5,4′-tetramethoxyl-α,β-diphenylethane-3′-O-sodium sulphate has good water solubility. By directional targeting, it pointedly affects tumor vessels without affecting non-tumor vessel, showing greater advantage over traditional chemotherapeutics that directly inhibit the growth of tumor cells as well as overcoming the limitations in toxic side effects and drug tolerance of traditional antineoplastic drugs. Antineoplastic research of it showed that 3,4,5,4′-tetramethoxyl-α,β-diphenylethane-3′-O-sodium sulphate not only can kill tumor cells, but according to joint administration experiment, it also remarkably enhances the efficacy of chemotherapeutics.